1. Technical Field
The present invention relates to a novel process for the preparation of R-sitagliptin and its pharmaceutical acceptable salts thereof. The present invention also provides structurally novel intermediates useful in the disclosed process, a pharmaceutical composition and a method of treating Type-2-diabetes.
2. Description of the Related Art
R-sitagliptin is commonly available as sitagliptin phosphate, 7-[(3R)-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazine phosphate (1:1) monohydrate, and has the following structural formula:

Sitagliptin phosphate is an orally administered dipeptidyl peptidase-4 (DPP-4) inhibitor. Sitagliptin has been developed for the treatment of Type-2-diabetes and is available in the market under the brand name JANUVIA® as tablets in the dosage strengths of 25, 50, or 100 mg equivalent base.
International Patent Publication WO2004087650 describes a process for the preparation of sitagliptin via benzyloxy protected tetrazolylpyrazine intermediate.
International Patent Publication WO2004085661 describes a process for the preparation of enantiomerically enriched sitagliptin via (S)-phenylglycine amide protected tetrazolyl pyrazine intermediate.
US PG Publication US20080058522 describes a process generically for the preparation of sitagliptin and its pharmaceutically acceptable salts using specific chiral bisphosphine ligands.
International Patent Publication WO2006081151 describes a process generically for the preparation of sitagliptin and its pharmaceutically acceptable salts using rhodium metal precursor complexed to a ferrocenyl diphosphine ligand.
US PG Publication US20060194977 describes a process for the preparation of Enantiomerically enriched sitagliptin using specific chiral ferrocenyl diphosphine ligands.
U.S. Pat. No. 6,699,871 describes various DPP-4 inhibitors including sitagliptin and their pharmaceutically acceptable salts, a pharmaceutical composition and method of treatment and a process for the preparation of sitagliptin hydrochloride as follows:

The aforementioned processes involve reactions that use specific chiral ligands or a stereo specific/stereoselective reduction process with specific stereoselective reducing agents, which are expensive and may not be commercially available, which may subsequently render the processes unsuitable on commercial scale.
Hence, there is a need for an improved process for the preparation of R-sitagliptin or its pharmaceutically acceptable salts which alleviates the problems associated with aforementioned processes as referred above.
The process of the present invention provides a process which is simple, ecofriendly, inexpensive, reproducible, robust and well suited on commercial scale.